The Selectide process is a random synthetic chemical library method based on the one-bead one-peptide (structure) concept. A "split-synthesis" method is used to generate huge random libraries (106-108). At the end of the synthesis, each bead expresses only one chemical entity (e.g., peptide). The whole library is then tested simultaneously for binding to a specific acceptor molecule of biologic interest. The ligand bead that interacts specifically with the acceptor molecule is then isolated for structure determination. Once a binding motif is identified, a secondary library (based on the motif of the primary screen) is generated and screened under a more stringent condition to identify leads of higher affinity. This process can be applied to both peptide and nonpeptide (small organic) libraries. In the case of nonsequencable structure libraries, the coding principle has to be applied for structure elucidation of positively reacting beads. Coding peptide is synthesized in parallel to the screening structure, and classical Edman degradation (one or multiple-step) is used for structural analysis. To exclude the possibility of interaction of the macromolecular target (e.g., receptor, enzyme, antibody) with the coding structure, a synthetic technique for segregation of the surface (screening structure) and the interior (coding structure) of the beads was developed. The one-bead one-structure process is invaluable in drug discovery for lead identification as well as further optimization of the initial leads. It also serves as an important research tool for molecular recognition.
ASJC Scopus subject areas
- Molecular Biology